Violence and Aggression

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Aggression has been related to specific biochemical processes in the brain. Can this type of research now be expanded to include the study of violence, assault, rape, robbery, homicide, suicide, child and elder abuse, and war? Should we search for "modifiable molecular manifestations" of these undesirable human traits? Should not biology join psychological, cultural, and political studies of war, to try to find out whether understanding of molecular processes in the brain might someday help decrease violence and war?

Beatings, gunshot wounds, and stabbings are clearly related to drugs and alcohol abuse. Drug traffickers and street dealers will go to any length, no matter how violent their behavior, to make money. Social factors include the prevalence of hostile environments, where children raise themselves on the streets, and view society as miserable and violent. They must be taught to accept responsibilities, and be respectful of authorities in order to escape the world of constant fear, terror, ignorance and envy. Without moral principles, they can never be free.

A better understanding of brain chemistry and its relation to behavior may facilitate addressing these societal factors. We can try to find out the influence of brain chemistry in producing violent behavior. We can detect regional biochemical difference in the brain between patients with depression and dementia (Fig 6.8).

In Parkinson's disease, there is degeneration of neurons in the substantia nigra. DA is deficient in the basal ganglia, especially the putamen, but also in the caudate nucleus. Administration of the DA precursor, L- dopa, to patients with Parkinson's disease increases DA synthesis, decreasing their difficulty in moving and stiffness, a striking example of how therapy can be based on detecting molecular abnormalities. Dopaminergic neurons in the frontal lobes are also involved in Parkinson's disease, resulting in difficulty in memory, attention, and problem solving. This shows how there is no clear-cut boundary between Parkinson's disease, and Alzheimer's disease. Problems are created by putting a patient in a single "diagnostic" category. Recently, efforts are being made to better characterize what is likely to be the patient's response to drug treatment. This is called personalized medicine.

Molecular imaging can examine the quantitative effects of drugs given to affect perception, learning, movement, memory, hallucinations, paranoia, anxiety, fear, rage, greed, arrogance, aggression, reward and punishment. Many drugs involve the dopaminergic, serotonergic, cholinergic, and opiate neurotransmitter systems. For example, scopol-amine and ACh affect language and memory. Hormones, including testosterone and estrogens, affect emotions, including aggressiveness and violent behavior.

PET and SPECT studies of the human brain are now widely used by the pharmaceutical industry in drug design, development, and regulatory approval. Drugs that bind to neurotransmitter receptors can be labeled with 18F- or 1 'C-, and their distribution was

Fig. 6.8 Statistical images showing the 18F- FDG images ofglucose utilization in the brains of patients with frontotemporal dementia (FTD); progressive supranuclear palsy (PSP); mild dementia of Alzheimer type (MID): and normal pressure hydrocephalus (NPH).

first imaged in mice, rats, or baboons; and then in normal humans; and eventually in patients with mental disorders, such as schizophrenia or depression. Biomarkers used by (1) FDA; (2) NIH; (3) academia; and (4) industry are based on assessing metabolism, cell proliferation, apoptosis, angiogenesis, cellular invasion, and intra- and intercellular communication.

Companies, including Siemens, General Electric (GE), and IBA, provide SPECT/CT and PET/CT instruments and cyclotrons for hospitals, universities, and pharmaceutical research laboratories. For example, at Yale University, there is a cyclotron, a GE 16 slice scanner, two GE 4 slice scanners, and one GE single slice scanner, all with helical capability. A 64-slice scanner was built in February 2006. The 64 slice scanner replaced a 4 slice scanner in the Emergency Department in October 2006.

Today, IBA's mini-cyclotrons are used all over the world. The most common products are 18O to provide 18F; 13N to provide UC; and 82Rb to provide 68Ga. In the latter case, the use of generators makes it possible to carry out studies away from the cyclotron. Three to 4 Curies of 18F- can be produced routinely by automated synthesis systems. uC-car-bon monoxide and nC-carbon dioxide are used in the labeling of many molecules.

In the future, small tabletop cyclotrons will be in every hospital or research laboratory together with kit-based microchemistry that allows rapid production of single doses of 18F- and 1 ^-radiotracers. Single dose production systems are based on microfluidic chemistry, which enables tiny drops of fluids to be manipulated on a silicon chip. A polytetrafluoroethylene matrix provides the basic element. Doses can be synthesized in one chemical step in 5-10 minutes in platforms producing a single tracer (Ron Nutt, Advanced Biomarker Technologies). We live in the Age of Simplification. Unfortunately, today the cost of development of a new radiotracer is close to $20 million each. In-house preparation of tracers will supplement the efforts of the 100 regional laboratories in the United States that provide 18F- FDG to hospitals.

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